Abstract Candida albicans is a commensal fungal pathogen that grows in yeast and hyphal forms in the human gut. C. albicans causes mucosal and cutaneous diseases that can result in significant mortality following systematic infections and it also exhibits drug resistance. Zebrafish have been an excellent model to investigate C. albicans infections because of their transparency and the availability of many transgenic lines. However, there is a limitation in using zebrafish as a model because the fish embryos cannot survive at 37°C therefore it is not suitable for studying Candida infections at physiological relevant human body temperature. In this thesis, the normal embryonic development of Arabian killifish (A. dispar) is investigated, revealing that embryogenesis was divided into 32 stages based on diagnostic patterns of development. A. dispar can also found to tolerate a wide range of temperatures and salinities. This suggests that A. dispar could be developed as a novel model to investigate host-pathogen interactions. The tolerance of A. dispar to high temperatures may in part be attributable to brown pigment cells with a highly fluorescent character that may have developed to allow the fish to adapt to live within extreme environmental conditions with strong sunlight and a wide range of temperatures (Chapter 3). In terms of Candida infections, this study examined A. dispar as a model to test C. albicans pathogenicity. The survival of A. dispar embryos following Candida infection showed a dose dependent relationship. We also found that A. dispar can survive longer than zebrafish after infection. Furthermore, C. albicans cells were observed to undergo a transition from yeast to hyphae at 37°C. An investigation of the ability of mutant strains of C. albicans with defects in cell wall mannosylation revealed a significant impact on virulence, host mortality, and the fishes’ immune response. The present study found that although the deletion of O- and N-mannan from the cell wall of C. albicans, affected fungal burden (attenuation), and the survival of the infected embryos per se was significantly decreased in the infections of the mutant strains compared to the WT. This data confirms the importance of the mannosylation state of the cell wall in triggering an immune recognition event (Chapter 4). A. dispar is also shown to be suitable for studying the effectiveness of 3 | P a g e antifungals. Fluconazole treatment of infected embryos and eggs promoted greater rates of survival at high doses, alongside a significant reduction of C. albicans CFUs (Chapter 4). When looking at the Candida-host interaction, we directly observed phagocytosed yeast cells within macrophages. Various detection methods were used to follow macrophages and neutrophils including Western blotting, immunostaining and histological staining (Sudan black and FITC-tyramide) allowing the monitoring of the time course of the immune cells. A biphasic response of macrophages was detected by L-plastin Western blotting, suggesting activation of two different type of macrophage: activated macrophage (M1) and alternative macrophage (M2). We also assayed reactive oxygen species (ROS) within infected embryos using a fluorescent probe (H2DCFDA), revealing the accumulation of the fluorescent probe at the sites of infection. Quantitative and qualitative analyses of the oxidative and immune response using the H2DCFDA and qPCR were also accomplished within A. dispar embryos after infection with both the WT and mutant strains of Candida albicans (WT, pmr1∆, mnt1-mnt2∆, and och1∆). The results confirmed that the mutant strains did not activate a host oxidative stress response nor immune cell accumulation when compared to WT, suggesting that the immune response is less activated against these mutants. Finally, a new transgenic line of A. dispar fish was developed using Betaactin-DsR-LoxP-GFP. The new transgenic A. dispar is suggested to be an ideal model for real time observation of host-pathogen interactions and for investigation of molecular functions of the immune response. Overall these results improve our understanding of the use of a new transparent fish model to study fungal pathogenesis and demonstrates the potential advantages of using this species in future studies of bacterial, fungal and viral pathogens at a physiologically relevant temperature for human infection. Such a model could lead us to investigate in more depth the key interactions between pathogens and their host and permit the screening and development of new antifungal therapies (that might target the pathogens directly or target the host immune system). View full metadata
Based on the assumption that the more teachers know about brain science, the better
prepared they will be to make instructional decisions.
Mind Mapping is a powerful tool for assisting any form of writing. Language is an
important device and a very beneficial means for human being to communicate with other
people .Writing is one of the language skills that will never be left in education.
The study aims at investigating the Impact of applying mind mapping technique as a prewriting
tool on Iraqi EFL college students in essay writing. To do so, 60 EFL college students
were divided randomly selected and divided into two groups experimental and control. Prior
to treatment, participants of the both groups were given a
The research work is "The passive voice as a grammatical phenomenon in four selected textbooks". The research deals with the grammatical phenomenon passive in German. The research consists of two parts, the theoretical and the empirical part. The present research work is divided into 3 sections:
The first section includes the definition of passive, passive types, process passive, state passive, passive with modal verbs, and other types of passive. The second section provides illustrations of the four selected textbooks. The third chapter presents the passive voice in textbooks, namely German language teaching for foreigners by Dora Schulz and Heinz Griesbach, Delfin von Aufderstrasse H. and others, Em von Balme, M. and others and
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The research aims to derive the efficient industrial plans for Al – shaheed public company under risk by using Target MOTAD as a linear alternative model for the quadratic programming models.
The results showed that there had been a sort of (trade- off) between risk and the expected gross margins. And if the studied company strives to get high gross margin, it should tolerate risk and vice versa. So the management of Al- Shaheed Company to be invited to apply the suitable procedures in the production process, in order to get efficient plans that improves it's performance .
Nonlinear time series analysis is one of the most complex problems ; especially the nonlinear autoregressive with exogenous variable (NARX) .Then ; the problem of model identification and the correct orders determination considered the most important problem in the analysis of time series . In this paper , we proposed splines estimation method for model identification , then we used three criterions for the correct orders determination. Where ; proposed method used to estimate the additive splines for model identification , And the rank determination depends on the additive property to avoid the problem of curse dimensionally . The proposed method is one of the nonparametric methods , and the simulation results give a
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The aim of the research is to identify the impact of the dimensions of the European Excellence Model in evaluating the performance of the bank of the research sample, as well as to interpret which dimensions are more important to the banks of the research sample. Based on the dimensions of this model, the United Bank for Investment and Finance has chosen a research community, and has met with officials of the United Bank for Investment and Finance at various administrative levels to measure the practices of excellence management in the European model, and the analytical approach has been the case study and the construction of the checklist as a tool to collect information. The research has reached the most important results There is a discr
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Globally, the COVID-19 pandemic’s development has presented significant societal and economic challenges. The carriers of COVID-19 transmission have also been identified as asymptomatic infected people. Yet, most epidemic models do not consider their impact when accounting for the disease’s indirect transmission. This study suggested and investigated a mathematical model replicating the spread of coronavirus disease among asymptomatic infected people. A study was conducted on every aspect of the system’s solution. The equilibrium points and the basic reproduction number were computed. The endemic equilibrium point and the disease-free equilibrium point had both undergone local stability analyses. A geometric technique was used
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